Full Press Release Details
Company Presentation October 2020
Disclaimer This presentation has been
prepared by AVROBIO, Inc. ("AVROBIO") for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on
studies, publications, surveys and other data obtained from third-party sources and AVROBIO's own internal estimates and research. While AVROBIO believes these third-party sources to be reliable as of the date of this presentation, it has not
independently verified, and AVROBIO makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. While AVROBIO believes its internal research is reliable, such research has not
been verified by any independent source. This presentation may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and
phrases such as "aims," "anticipates," "believes," "could," "designed to," "estimates," "expects," "forecasts," "goal,"
"intends," "may," "plans," "possible," "potential," "seeks," "will," and variations of these words and phrases or similar expressions that are intended to identify
forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates; the design, commencement,
enrollment and timing of ongoing or planned clinical trials and regulatory pathways; the timing of patient recruitment and enrollment activities, clinical trial results, and product approvals; the timing of our ongoing preclinical studies; the
anticipated benefits of our gene therapy platform including the potential impact on our commercialization activities, timing and likelihood of success; the expected benefits and results of our implementation of the plato platform in our
clinical trials and gene therapy programs; the expected safety profile of our investigational gene therapies; the potential impact of the COVID-19 outbreak on our clinical trial programs and business generally, as well as our plans and expectations
with respect to the timing and resumption of any development activities that may be temporarily paused as a result of the COVID-19 outbreak; the market opportunity for and anticipated commercial activities relating to our investigational gene
therapies; and statements regarding our financial and cash position and expected cash runway. Any such statements in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. Any forward-looking
statements in this presentation are based on our current expectations, estimates and projections about our industry as well as management's current beliefs and expectations of future events only as of today and are subject to a number of risks
and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more
of our product candidates will not be successfully developed or commercialized; the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators; the risk that we may not successfully recruit or enroll a
sufficient number of patients for our clinical trials; the risk that we may not realize the intended benefits of our gene therapy platform, including the features of our plato platform; the risk that our product candidates or procedures in
connection with the administration thereof will not have the safety or efficacy profile that we anticipate; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will
not be replicated or will not continue in ongoing or future studies or trials involving our product candidates; the risk that we will be unable to obtain and maintain regulatory approval for our product candidates; the risk that the size and growth
potential of the market for our product candidates will not materialize as expected; risks associated with our dependence on third-party suppliers and manufacturers; risks regarding the accuracy of our estimates of expenses and future revenue; risks
relating to our capital requirements and needs for additional financing; risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may
materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises; and risks relating to our ability to obtain and maintain intellectual property
protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO's actual results to differ from those contained in the forward-looking
statements, see the section entitled "Risk Factors" in AVROBIO's most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO's subsequent filings
with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Note regarding trademarks: plato is a registered trademark of AVROBIO. Other
trademarks referenced in this presentation are the property of their respective owners. Note regarding future updates: The statements contained in this presentation reflect our current views with respect to future evets, which may change
significantly as the global consequences of the COVID-19 pandemic rapidly develop. Accordingly, we do not undertake and specifically disclaim any obligation to update any forward-looking statements.
Our mission: Giving people with genetic
disease freedom for life
Proof-of-Concept IND-Enabling Phase 1/2
Commercial Rights Fabry AVR-RD-01 AVROBIO Cystinosis AVR-RD-04 AVROBIO Gaucher AVR-RD-02 AVROBIO Hunter AVR-RD-05 AVROBIO Pompe AVR-RD-03 AVROBIO Preclinical Multiple programs in the clinic Phase 2 Phase 1/2 Phase 1/2 12 patients dosed to date
across three indications IND: Investigational New Drug Preclinical
Addressing multi-billion dollar market
opportunity Disease Est. Cost Per Patient Per Year Approx. 2019 Net Sales Selected Companies Fabry $1.4B Gaucher $1.4B Pompe $1.0B Cystinosis $0.2B CURRENT STANDARD OF CARE COSTS Sources: Rombach S et al, Orphanet J Rare Dis, 2013; van Dussen L et
al, Orphanet J Rare Dis, 2014; WAC pricing from Redbook; 2019 Net Sales from company annual and other reports * for Horizon's Procysbi oral therapy (delayed release cysteamine bitartrate) Note: Shire acquired by Takeda in 2019 $320k $250k-400k
Lifelong treatments vs. potential
single-dose therapy Treatment burden Enzyme or protein level DISEASE PROGRESSION CONTINUES DISEASE PROGRESSION COULD HALT OR REVERSE Enzyme Replacement Therapy (ERT) Temporary bolus of enzyme, not curative Bi-Weekly ERT Plasma Pharmacokinetics of
ERT Life-long infusions Transient, intermittent elevation Bi-weekly IV infusions AVROBIO Gene Therapy Designed for 24/7 expression of protein, curative potential Functional Protein Expression in Transduced HSCs and Their Progeny 24/7 expression
One-Time Gene Therapy Long-term, continuous elevation Single IV infusion ERT: Enzyme Replacement Therapy; IV: Intravenous; HSC: Hematopoietic Stem Cells
Established ex vivo lentiviral approach
Transduce with lentiviral vector carrying therapeutic gene GENE THERAPY APPROACH Select CD34+ stem cells Collect mobilized blood 3 2 1 Harvest and freeze 4 Condition and dose 5
Fabry Disease AVR-RD-01
Goals for gene therapy in Fabry disease
UNMET NEEDS: Kidney function Unmet needs: proteinuria, polyuria, kidney failure Cardiac function Unmet needs: left ventricular hypertrophy, fibrosis, heart failure Neuropathic pain Unmet needs: pain and burning sensations in hands and feet, pain
crises Everyday burden of illness and life expectancy Unmet needs: fatigue, inability to sweat, joint pain, abdominal pain, diarrhea, vomiting, cloudy vision, hearing loss, tinnitus, rash, angiokeratomas, biweekly infusions, shortened lifespan CNS
complications Unmet needs: TIA/stroke, depression, impaired executive function, white matter hyperintensities Sources: Wanner C et al, Med Genetics and Metab, 2018; Burlina A, JIEMS, 2016 CNS: Central Nervous System; TIA: Transient Ischemic
Two AVR-RD-01 Fabry clinical trials
9 patients dosed across Phases 1 and 2 PHASE 1 Investigator-Sponsored Trial* PHASE 2 AVRO - FAB-201 Trial Patients Patients Key Objective Key Objectives n = 5 (fully enrolled) On ERT > 6 months prior to enrollment 18 - 50 year-old males n =
8-12 (4 patients dosed to-date) Treatment-naive 16 - 50 year-old males Safety and preliminary efficacy Safety and efficacy FAB-201 = AVRO-RD-01-201 Study * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ERT:
Enzyme Replacement Therapy
PATIENT 1 PATIENT 2 PATIENT 3
PATIENT 4 Age of symptom onset / diagnosis 10 / 19 years 36 / 37 years 13 / 13 years 9 / 9 years Age dosed with AVR-RD-01 21 years 46 years 40 years 26 years Mutation c.1021G>A (p.E341K) c.644A>G (p.N215S) c.639+1G>T c.833dupA Primary
disease signs and symptoms Kidney disease Chronic pain GI symptoms Decreased cold sensation Cardiac disease Peripheral neuropathy Chronic pain Increased tiredness GI symptoms Intermittent tinnitus Mild high frequency hearing loss Raynaud's
syndrome Kidney disease GI symptoms Peripheral neuropathy Bilateral deafness Tinnitus Peripheral edema Decreased cold sensation Chronic pain Peripheral neuropathy Neuropathic shuffling gait Lethargy Temperature intolerance Tinnitus Hearing loss GI
symptoms Leukocyte AGA enzyme activity at baseline (nmol/hr/mg protein) 0.10* 2.38** 0.58** 0.46** Plasma lyso-Gb3 at baseline (nM) 202*** 8*** 147*** 92*** Comment IgA deposits in kidney biopsy Cardiac variant, not a classic Fabry male Fabry
FAB-201 Patient Characteristics Treatment-na ve Fabry patients * Mayo Lab, ref range 23.1 nmol/hr/mg protein ** Rupar Lab, ref range 24-56 nmol/hr/mg protein *** Reference value 2.4 nM AGA: galactosidase A;
Lyso-Gb3: Globotriaosylsphingosine; GI: Gastrointestinal; IgA: Immunoglobulin-A
Patient 1: 87% substrate reduction
in kidney biopsy at 1 year Average number of Gb3 inclusions per peritubular capillary (PTC) Baseline 1 Year (48 weeks) 3.55 0.47 Unpaired t-test for difference between n=55 PTCs at baseline vs. n=101 PTCs at 1 year; p < 0.0001 Error bar
represents the standard deviation 3.55 Mean Number of Gb3 Inclusions per PTC Baseline: The last available, non-missing observation prior to AVR-RD-01 infusion Note: With respect to Fabry disease, Gb3 inclusions per PTC is interchangeable with GL-3
inclusions per KIC FAB-201-1: First patient in FAB-201 clinical trial PTC: Peritubular Capillary; Gb3: Globotriaosylceramide; GL-3: Globotriaosylceramide; KIC: Kidney Interstitial Capillary FAB-201 FABRY PHASE 2
VCN/Diploid Genome - PBMCs Infuse
AVR-RD-01 Day 0 Patient 1: Sustained response across multiple measures up to 22 months Drug Product VCN/dg: 0.7 KIDNEY FUNCTION remains within normal range at 12 mos. CARDIAC FUNCTION remains within normal range at 12 mos. *Source:
https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Source: Alfakih K et al, J Magn Reson Imaging, 2003 EF: Ejection Fraction; LV: Left Ventricular mGFR mL/min/1.73 m2 eGFR
mL/min/1.73 m2 Baseline Month 12 Normal Range mGFR/eGFR Average 116* mL/min/1.73 m2 Male (20-39 years) Reference Range Mean Values SD 64.3 4.2% 138.9 24.5 g 67.8 10.7 g/m2 Male (20-39 years) EF (%) LV Mass
(Absolute) (g) LV Mass Index (Normalized) (g/m2) Baseline Month 12 FAB-201 FABRY PHASE 2 VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells Lyso-Gb3 Plasma Reference Value: 2.4 nM; Total Gb3 Plasma Reference Value: 4961 nM; 6012 nM
before August 2018 (until Day 28 for Patient 1) Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Vector Copy Number (VCN) Lyso-Gb3 Plasma (nM) Total Gb3 Plasma (nM) Infuse AVR-RD-01 Day 0 Estimated Glomerular Filtration Rate Leukocyte
AGA Activity (nmol/hr/mg protein) Plasma AGA Activity (nmol/hr/mL) Infuse AVR-RD-01 Day 0 Plasma AGA Missing Plasma AGA Analysis Leukocyte AGA Total Gb3 Lyso-Gb3 eGFR: Estimated Glomerular Filtration Rate Infuse AVR-RD-01 Day 0 Plasma Lyso-Gb3 and
Total Gb3 Leukocyte + Plasma AGA Enzyme Activity Lab A: Mayo Clinic Laboratories; Lab B: Rupar Laboratory; Lab A Leukocyte AGA Activity Reference Range: >23.1 nmol/hr/mg protein; Lab B Reference Range: 24-56 nmol/hr/mg protein; Plasma AGA
Activity Reference Range: 5.1-9.2 nmol/hr/mL; AGA: -galactosidase A
VCN/Diploid Genome - PBMCs Infuse
AVR-RD-01 Day 0 Infuse AVR-RD-01 Day 0 Lyso-Gb3 Plasma (nM) Total Gb3 Plasma (nM) Patient 2: Sustained response across multiple measures up to 18 months Drug Product VCN/dg: 0.5 VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells
KIDNEY FUNCTION remains within normal range mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 EF (%) LV Mass (Absolute) (g) LV Mass Index (Normalized) (g/m2) Baseline Month 12 Source: https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular
Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Source: Maceira AM et al, J of Cardiovascular Magnetic Resonance, 2006 EF: Ejection Fraction; LV: Left Ventricular Reference Range Mean Values Male 40-49 years 58-75% 58-91 g/m2
Baseline Month 12 Normal Range mGFR/eGFR Average 99 mL/min/1.73 m2 Male (40-49 years) CARDIAC FUNCTION remains within normal range FAB-201 FABRY PHASE 2 - Cardiac Variant Total Gb3 Lyso-Gb3 Lyso-Gb3 Plasma Reference Value: 2.4 nM; Total
Gb3 Plasma Reference Value: 4961 nM; Note: Patient #2 has normal substrate, consistent with late-onset cardiac variant phenotype; Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Vector Copy Number (VCN) Plasma Lyso-Gb3 and Total Gb3
Leukocyte + Plasma AGA Enzyme Activity Leukocyte AGA Activity Reference Range: 24-56 nmol/hr/mg protein; Plasma AGA Activity Reference Range: 5.1-9.2 nmol/hr/mL; AGA: -galactosidase A Leukocyte AGA Activity (nmol/hr/mg protein)
Plasma AGA Activity (nmol/hr/mL) Infuse AVR-RD-01 Day 0 eGFR: Estimated Glomerular Filtration Rate Plasma AGA Leukocyte AGA Infuse AVR-RD-01 Day 0 Estimated Glomerular Filtration Rate *1-year / "Month 12" = 48 weeks per protocol 108 -
VCN/Diploid Genome - PBMCs Infuse
AVR-RD-01 Day 0 Infuse AVR-RD-01 Day 0 Lyso-Gb3 Plasma (nM) Total Gb3 Plasma (nM) Infuse AVR-RD-01 Day 0 Leukocyte AGA Activity (nmol/hr/mg protein) Plasma AGA Activity (nmol/hr/mL) FAB-201 FABRY PHASE 2 Vector Copy Number (VCN) VCN: Vector Copy
Number; PBMCs: Peripheral Blood Mononuclear Cells Plasma Lyso-Gb3 and Total Gb3 Lyso-Gb3 Plasma Reference Value: 2.4 nM; Total Gb3 Plasma Reference Value: 4961 nM; Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Leukocyte + Plasma AGA
Enzyme Activity KIDNEY FUNCTION remains within normal range Source: https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Reference Range Mean Values Male 40-49 years
58-75% 58-91 g/m2 Normal Range mGFR/eGFR Average 99 mL/min/1.73 m2 Male (40-49 years) CARDIAC FUNCTION remains within normal range Baseline Month 12 mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 EF (%) LV Mass (Absolute) (g) LV Mass
Index (Normalized) (g/m2) Baseline Month 12 Drug Product VCN/dg: 1.4 Plasma AGA Leukocyte AGA Estimated Glomerular Filtration Rate eGFR (mL/min/1.73m2) Infuse AVR-RD-01 Day 0 Patient 3: Sustained response across multiple measures up to 1 year*
*1-year / "Month 12" = 48 weeks per protocol Leukocyte AGA Activity Reference Range: 24-56 nmol/hr/mg protein; Plasma AGA Activity Reference Range: 5.1-9.2 nmol/hr/mL; AGA: -galactosidase A Total Gb3 Lyso-Gb3 eGFR:
Estimated Glomerular Filtration Rate 108 - 185 g Source: Maceira AM et al, J of Cardiovascular Magnetic Resonance, 2006 EF: Ejection Fraction; LV: Left Ventricular
FAB-201 FABRY PHASE 2 Patients 1-4:
Leukocyte and plasma enzyme activity sustained up to 22 months Patient #4 dosed using plato Plasma AGA Activity (nmol/hr/mL) Leukocyte AGA Activity (nmol/hr/mg protein) Leukocyte AGA Activity Reference Range: 24-56 nmol/hr/mg protein;
Plasma AGA Activity Reference Range: 5.1-9.2 nmol/hr/mL; AGA: -galactosidase A Patient 1 Patient 2 Patient 3 Patient 4
Reduction from Baseline to Last
Observation Patient 1 86% Patient 2 NA Patient 3 49% Patient 4 59% Lyso-Gb3 Plasma Reference Value: 2.4 nM; Lyso-Gb3: Globotriaosylsphingosine Note: Patient #2 has normal substrate, consistent with late-onset cardiac variant phenotype FAB-201 FABRY
PHASE 2 Patients 1-4: Plasma lyso-Gb3 reduction sustained up to 22 months Patient 1 Patient 2 Patient 3 Patient 4
FAB-201 FABRY PHASE 2 Patients 1-4:
VCN stable up to 22 months Patient #4 dosed using plato Patient 1 Patient 2 Patient 3 Patient 4 Drug Product VCN/dg Patient 1 0.7 Patient 2 0.5 Patient 3 1.4 Patient 4 1.6 VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear
Two AVR-RD-01 Fabry clinical trials
PHASE 1 Investigator-Sponsored Trial* Patients Patients Key Objectives Key Objectives n = 5 (fully enrolled) On ERT > 6 months prior to enrollment 18 - 50 year-old males n = 8-12 (4 patients dosed to-date} Treatment-naive 16 - 50 year-old males
Safety and preliminary efficacy Safety and efficacy PHASE 2 AVRO - FAB-201 Trial 9 patients dosed across Phases 1 and 2 FAB-201 = AVRO-RD-01-201 Study * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ERT:
Enzyme Replacement Therapy
PATIENT 1 PATIENT 2 PATIENT 3